Adrenergic lipolysis in human fat cells: properties and physiological role of alpha-adrenergic receptors (author's transl)

Lipolytic activity of human isolated fat cells from different fat deposits was studied. The purpose of the present investigations was to determine the epinephrine responsiveness, with regard to alpha- and beta-adrenergic receptor site activity, of omental and subcutaneous adipocytes (abdominal or from the lateral part of the thigh). Adipocytes were obtained from normal subjects or from obese subjects on iso- or hypocaloric diets. The lipolytic effect of epinephrine varied according to the fat deposits, while the beta-lipolytic effect of isoproterenol was more stable (Fig. 1). We explored the possible involvement of adrenergic alpha-receptors, in order to explain these results. The potentiating action of phentolamine on epinephrine-induced lipolysis, and the antilipolytic effect of alpha-agonists on basal or theophylline--induced lipolysis, were found to be a good indication of alpha-adrenergic activity. The alpha-adrenergic antilipolytic effect was most prominent in adipose tissue from the lateral part of the thigh, and less noticeable in omental adipocytes. In conclusion, the inability of epinephrine to induce lipolysis, and the epinephrine-induced inhibition of lipolysis observed when the basal rate of FFA release was spontaneously increased in subcutaneous fat-cells of the thigh, could be explained by an increased alpha adrenergic responsiveness (Fig. 2). Moreover, various alpha-adrenergic agonists (phenylephrine, noradrenaline and adrenaline) showed a clear inhibiting effect on theophylline-stimulated adipocytes from the thigh. The pharmacological study of the antilipolytic effect of epinephrine on theophylline-induced lipolysis showed that the inhibition was linked to a specific stimulation of the alpha-receptors of the subcutaneous adipocytes (Fig. 4). From the different sets of experiments, it is shown that the modifications in the lipolytic effect of epinephrine on adipocytes of different areas could be explained by the occurrence of a variable alpha-adrenergic effect initiated by catecholamine. Furthermore, theophylline stimulation of lipolysis provides an accurate system to investigate the alpha-inhibiting effect of catecholamines. Our study was completed by the investigation of the lipolytic activity of subcutaneous fat cells from obese subjects submitted to a hypocaloric diet (800-1 000 Cal/day). An increased alpha-inhibitory effect of epinephrine was shown on the increased basal lipolytic activity observed in the fat cells of obese subjects on a hypocaloric diet (Fig. 5); a similar effect was observed when these adipocytes were stimulated by theophylline. To conclude, these investigations allow the alpha-adrenergic effect to be considered as a regulator mechanism of the in vitro lipolytic activity in human adipose tissue, since the antilipolytic effect is operative whenever the basal rate of lipolysis is increased (spontaneously, after caloric restriction, or with a lipolytic agent such as theophylline).     

Identification of alpha-2 adrenergic receptors in rabbit adipocytes

Adrenaline, an alpha and beta adrenergic agonist don't modify theophylline induced lipolysis in perirenal and epididymal adipose tissue of the rabbit. Clonidine an alpha 2 adrenergic agonist inhibits theophylline stimulated lipolysis in the two tissue indicating the existence of alpha 2 adrenergic responsiveness. Direct identification of these receptors by radioligand binding studies shows that (H3) yohimbine an alpha 2 adrenergic antagonist binds to rabbit's fat cell membranes with high affinity: KD = 1.7 +/- 0.1 nmoles. The maximal number of binding sites at saturation is low 16 +/- 29 fmoles/mg protein.     

Adrenergic control of lipogenesis and lipolysis in the chicken in vitro

The adrenergic inhibition of lipogenesis and stimulation of lipolysis in the avian has been examined using chicken hepatocytes and adipose tissue explants in vitro. Lipogenesis was inhibited by adrenergic agonists: epinephrine (alpha + beta) greater than isoproterenol (beta 1/beta 2) greater than norepinephrine (alpha 1/alpha 2, beta 1) greater than metaproterenol (beta 2), phenylephrine (alpha 1). Dobutamine (beta 1 agonist) and dopamine (dopaminergic agonist) did not significantly affect [14C]acetate incorporation into lipid, while clonidine and para-aminoclonidine (alpha 2 agonists) were slightly stimulatory. Lipolysis in young and adult chicken adipose tissue was stimulated by epinephrine, isoproterenol, phenylephrine, dobutamine and metaproterenol, but was inhibited by clonidine and para-aminoclonidine. Both the antilipogenic and lipolytic effects of epinephrine were partially blocked by phentolamine (alpha 1 = alpha 2 antagonist) or propranolol (beta 1 = beta 2 antagonist), but completely inhibited by phentolamine and propranolol administered together.     

Adrenergic regulation of adipocyte metabolism

Adipocytes can be readily isolated from intact adipose tissue. In adipocytes from hamster and human white adipose tissue it is possible to demonstrate beta, alpha 1, and alpha 2 adrenoceptors. Alpha 2 adrenoceptor activation inhibits while beta adrenoceptor activation stimulates cyclic AMP accumulation and lipolysis. The effects of catecholamines on cyclic AMP accumulation are mediated through regulation of adenylate cyclase activity, which is activated through beta adrenoceptors and inhibited through alpha 2 adrenoceptors. Activation of alpha 1 adrenergic receptors has been shown to be associated with elevations of cytosol calcium and increased turnover of phosphatidylinositol. In white adipocytes, the only known alpha 1 adrenergic effects are inhibition of glycogen synthase and stimulation of glycogen phosphorylase via mechanisms distinct from those by which cyclic AMP produces similar end effects. In brown adipocytes, alpha 1 adrenoceptor activation stimulates respiration. Thyroid hormones primarily regulate the sensitivity of adipocytes to beta-adrenergic amines while having little effect on alpha adrenoceptor sensitivity.     

Dissociation of the effect of adrenalin on glucose uptake from that on adenosine cyclic 3′,5′-monophosphate levels and on lipolysis in rat-isolated fat cells

The effects of the adrenergic blocking agents phenoxybenzamine, phentolamine, indoramin and propranol on adrenalin-stimulated glucose uptake, lipolysis and cyclic AMP formation have been studied in rat-isolated fat cells. The β-adrenergic blocking agent propranolol was found to inhibit adrenaline-stimulated lipolysis and cyclic AMP formation at concentrations which did not inhibit adrenalin-stimulated glucose uptake. Conversely, the α-adrenergic blocking agent phenoxybenzamine inhibited adrenalin-stimulated glucose uptake at concentrations which did not inhibit lipolysis and cyclic AMP formation. The α-adrenergic blocking agents phentolamine and indoramin did not show differential effects on adrenalin-stimulated lipolysis and glucose uptake. Phenoxybenzamine had no effect on glucose uptake stimulated by insulin, adrenocorticotropic hormone and dibutyryl cyclic AMP. It is suggested that a substantial proportion of adrenalin-stimulated glucose uptake in rat-isolated fat cells is mediated by a mechanism not involving cyclic AMP. The adrenalin receptor was apparently α in type although the lack of effects of phentolamine and indoramin were not typical of those described on other α-systems.     

Acute exposure to long-chain fatty acids impairs {alpha}2-adrenergic receptor-mediated antilipolysis in human adipose tissue

The acute in vitro and in vivo effects of long-chain fatty acids (LCFAs) on the regulation of adrenergic lipolysis were investigated in human adipose tissue. The effect of a 2 h incubation, without or with LCFA (200 mumol/l), on basal and hormonally induced lipolysis was tested in vitro on isolated fat cells. The lipolytic response to epinephrine was enhanced by suppression of the antilipolytic alpha(2)-adrenergic effect. Then, healthy lean and obese male subjects performed a 45 min exercise bout at 50% of their heart rate reserve either after an overnight fast or 3 h after a high-fat meal (HFM: 95% fat, 5% carbohydrates). Subcutaneous adipose tissue lipolysis was measured by microdialysis in the presence or absence of an alpha-antagonist (phentolamine). In vivo, a HFM increased plasma levels of nonesterified fatty acids in lean and obese subjects. In both groups, the HFM did not alter hormonal responses to exercise. Under fasting conditions, the alpha(2)-adrenergic antilipolytic effect was more pronounced in obese than in lean subjects. The HFM totally suppressed the alpha(2)-adrenergic antilipolytic effect in lean and obese subjects during exercise. LCFAs per se, in vitro as well as in vivo, suppress alpha(2)-adrenergic-mediated antilipolysis in adipose tissue. LCFA-mediated suppression of antilipolytic pathways represents another mechanism whereby a high fat content in the diet might increase adipose tissue lipolysis.     

Adrenergic control of lipolysis in swine adipose tissue

Most potential adrenergic compounds did not stimulate lipolysis in swine adipose tissue slices. Most of the sympatholytic agents antagonized lipolysis. Most beta 1- and beta 2-adrenergic agonists were not active but many were active with rat adipose tissue. Catecholamines (epinephrine, norepinephrine and isoproterenol), the resorcinol containing beta 2-agonists (terbutaline, metaproterenol and fenoterol) and the beta 1-agonist, dobutamine were active. The beta 1-antagonists were generally more potent and efficacious than the beta 2-antagonists. The swine adipose tissue adrenoceptor was not readily classified as either beta 1- or beta 2-specific.     

Human fat cell beta-adrenergic receptors: beta-agonist-dependent lipolytic responses and characterization of beta-adrenergic binding sites on human fat cell membranes with highly selective beta 1-antagonists

Beta-adrenergic receptors were characterized in human fat cell membranes using 125I-labeled cyanopindolol (125I-labeled CYP) and highly selective beta 1-antagonists. The iodinated radioligand bound saturably and specifically to a single class of high affinity binding sites. The number of binding sites determined with 125I-labeled CYP closely agreed with that determined with two other tritiated radioligands: [3H]dihydroalprenolol and [3H]CGP-12,177. Since 125I-labeled CYP does not discriminate between beta 1- and beta 2-adrenoceptors, the densities of the two receptor subtypes were determined from the competition curves of 125I-labeled CYP by highly selective beta 1-antagonists (bisoprolol, ICI-89,406, CGP-20,712A, and LK-204,545). Moreover, in order to enable correlation with binding data, the regulation of adenylate cyclase activity and of lipolysis was tested with various beta-agonist and antagonist compounds. The results obtained on fat cell membranes from abdominal subcutaneous adipose tissue demonstrated the following. 1) 125I-labeled CYP represents a valuable tool for the quantification and the delineation of beta-receptor subtypes. 2) The presence of sodium ions in binding buffers causes a modification of the affinity of beta-sites for some beta-antagonists. 3) The human fat cell beta adrenergic receptor population defined by nonselective radioligands is composed of two subtypes that can be interpreted in terms of classic beta 1- and beta 2-adrenergic receptor subtypes as assessed by competition studies with highly selective antagonists; beta 2-sites are predominant (60-70% of 125I-labeled CYP sites) in the adipocytes of slightly overweight women. 4) Results support the idea that beta 1- as well as beta 2-adrenergic receptors are coupled with adenylate cyclase and involved in the induction of lipolysis. 5) The results focus on the interest in some beta 2-agonist drugs (zinterol, clenbuterol) as partial inductors of lipolysis, with the lipolytic efficacies of these compounds being well correlated with their efficacies at 125I-labeled CYP sites.     

Effects of testosterone on fat cell lipolysis. Species differences and possible role in polycystic ovarian syndrome

Testosterone is a potent regulator of lipolysis by influencing catecholamine signal transduction in fat cells. Major species differences exist as regards the testosterone effect. In rodents testosterone increases beta-adrenergic receptor mediated signals to lipolysis at multiple steps in the lipolytic cascade. The sex hormone also increases alpha2-adrenoceptor antilipolytic signalling in hamster which unlike rat express this receptor in their fat cells. In humans the region of adipose tissue is critical. Visceral fat cell lipolysis is not responsive to testosterone but this sex hormone decreases catecholamine-induced lipolysis in subcutaneous fat cells due to inhibition of the expression of beta2-adrenoceptors and hormone sensitive lipase. In polycystic ovarian syndrome (PCOS), which is characterized as a hyperandrogenic state, the lipolytic effect of catecholamine is decreased in subcutaneous adipocytes due to low content of beta2-adrenoceptors and hormone sensitive lipase. It is possible that the increased testosterone levels are responsible for these abnormalities in catecholamine signal transduction in subcutaneous fat cells of PCOS women. However, in visceral fat cells of PCOS women catecholamine-induced lipolysis is enhanced which cannot be explained by testosterone.     

Natriuretic peptides: a new lipolytic pathway in human adipocytes.

Atrial natriuretic peptide (ANP) receptors have been described on rodent adipocytes and expression of their mRNA is found in human adipose tissue. However, no biological effects associated with the stimulation of these receptors have been reported in this tissue. A putative lipolytic effect of natriuretic peptides was investigated in human adipose tissue. On isolated fat cells, ANP and brain natriuretic peptide (BNP) stimulated lipolysis as much as isoproterenol, a nonselective beta-adrenergic receptor agonist, whereas C-type natriuretic peptide (CNP) had the lowest lipolytic effect. In situ microdialysis experiments confirmed the potent lipolytic effect of ANP in abdominal s.c. adipose tissue of healthy subjects. A high level of ANP binding sites was identified in human adipocytes. The potency order defined in lipolysis (ANP > BNP > CNP) and the ANP-induced cGMP production sustained the presence of type A natriuretic peptide receptor in human fat cells. Activation or inhibition of cGMP-inhibited phosphodiesterase (PDE-3B) (using insulin and OPC 3911, respectively) did not modify ANP-induced lipolysis whereas the isoproterenol effect was decreased or increased. Moreover, inhibition of adenylyl cyclase activity (using a mixture of alpha(2)-adrenergic and adenosine A1 agonists receptors) did not change ANP- but suppressed isoproterenol-induced lipolysis. The noninvolvement of the PDE-3B was finally confirmed by measuring its activity under ANP stimulation. Thus, we demonstrate that natriuretic peptides are a new pathway controlling human adipose tissue lipolysis operating via a cGMP-dependent pathway that does not involve PDE-3B inhibition and cAMP production.     

Effect of nitric oxide donors on isoprenaline-induced lipolysis in rat epididymal adipose tissue: studies in isolated adipose tissues and immobilized perfused adipocytes

The present investigation was directed to study the effect of in vitro or ex vivo NO donors, sodium nitroprusside and molsidomine, using isolated sliced adipose tissue or in the form of immobilized and perfused adipocytes on the basal and isoprenaline-stimulated lipolysis. The results demonstrated that 1) in vitro application of sodium nitroprusside to perfused adipocytes or molsidomine to sliced adipose tissues affects isoprenaline-induced lipolysis in two ways, an increase in lipolysis at low isoprenaline concentrations (which means the sensitization of adipose tissues to adrenergic effect by NO) and decreased adrenergic agonist-stimulated lipolysis at higher concentration of isoprenaline (a decrease in the maximum lipolytic effect of isoprenaline), 2) low concentrations of molsidomine alone induced lipolysis from adipose tissue which attained more than 60% of that by isoprenaline (pD2 value for molsidomine = 11.2, while pD2 for isoprenaline = 8.17) while sodium nitroprusside did not affect the basal lipolysis significantly, 3) in vivo administration of molsidomine for 2 days reduced the maximum lipolytic effect of isoprenaline and (only non-significantly) increased the sensitivity to low doses of isoprenaline. In conclusion the present data demonstrate that NO plays an important role in adrenergic lipolysis in adipose tissues and further investigations are needed to unravel the exact role of NO in lipolysis.     

Roles of alpha and beta adrenergic receptors in control of glucose oxidation in hamster epididymal adipocytes.

Oxidation of [14C] glucose in isolated epididymal adipocytes from Golden hamsters was stimulated by isoproterenol, epinephrine and norepinephrine, which all interact with beta-adrenergic receptors and by adrenocorticotrophic hormone. In contrast alpha-receptor agonists, such as phenylephrine, methoxamine or clonidine did not increase basal glucose oxidation. The beta-adrenergic blocking drug propranolol inhibited both lipolysis and glucose oxidation when these had been stimulated by isoproterenol, epinephrine or norepinephrine. Conversely, the alpha-adrenergic blocking drugs phentolamine and phenoxybenzamine did not influence lipolysis or glucose oxidation when isoproterenol provided the stimulus and increased both lipolysis and glucose metabolism in the present of either epinephrine or norepinephrine. All alpha-adrenergic agonists tested (phenylephrine, methoxamine and clonidine) lowered lipolysis and glucose oxidation isolated adipocytes exposed to isoproterenol. However, when adrenocorticotropin provided the stimulus for glucose oxidation and lipolysis, only clonidine produced a significant reduction in lipolysis and glucose oxidation. None of the alpha-agonists influenced glucose metabolism which had been increased by insulin. These data confirm the presence of both alpha and beta adrenergic receptors on hamster epididymal adipocytes and suggest that they exert antagonistic influences on lipolysis and glucose oxidation. These data are also consistent with the view that adrenergic stimulation of glucose oxidation and lipolysis in adipocytes are both mediated through beta receptors.     

Inhibition of adenosine 3':k'-monophosphate accumulation white fat acids, lactate, and beta-hydroxybutyrate.

The large increase in cyclic AMP accumulation by rat white fat cells seen in the presence of lipolytic agents plus methylxanthines and adenosine deaminase was markedly inhibited by lactate. However, lipolysis was unaffected by lactate. Octanoate, hexanoate, heptanoate, and beta-hydroxybutyrate inhibited both cyclic AMP accumulation and lipolysis by rat fat cells. The mechanism by which these acids inhibit lipolysis differs from that for long chain fatty acids such as oleate. Oleate directly inhibited triglyceride lipase activity of homogenized rat adipose tissue. In contrast, octanoate, beta-hydroxybutyrate, and lacatate had no effect on triglyceride lipase activity. Hormone-stimulated adenylate cyclase activity of rat fat cell ghosts was inhibited by oleate and 4mM octanoate but not by 1.6 mM octanoate, heptanoate, hexanoate, beta-hydroxybutyrate or lactate. None of the acids affected the soluble protein kinase activity of rat adipose tissue. There was no stimulation by lactate, butyrate, beta-hydroxybutyrate, or octanoate of the soluble or particulate cyclic AMP antilipolytic action of a short chain acid such as octanoate or hexanoate was not accompanied by any drop in total fat cell ATP. The mechanism by which lactate lowers cyclic AMP but not lipolysis remains to be established.     

Increased norepinephrine by medium-chain triglyceride attributable to lipolysis in white and brown adipose tissue of C57BL/6J mice

A further investigation of the lipolysis induced by medium-chain triglyceride (MCT) was conducted on C57BL/6J mice fed with a diet containing 2% MCT or 2% long-chain triglyceride (LCT). Blood norepinephrine, body fat and blood lipid variables, and the protein or mRNA expression of the genes relevant to lipolysis were measured and analyzed in the white and brown adipose tissue (WAT, BAT). Decreased body fat and improved blood lipid profiles attributable to MCT were confirmed. A higher level of blood norepinephrine was observed with the MCT diet. The adipose triglyceride lipase (ATGL) activity and its mRNA expression, the expression of protein and mRNA of the beta 3 adrenergic receptor (β3-AR) in both WAT and BAT, and the hormone-sensitive lipase (HSL) activity and its mRNA expression in BAT were significantly increased in the mice with MCT feeding. The lipolysis induced by MCT might be partially mediated by increasing norepinephrine, thereafter signaling the up-regulation of β3-AR, ATGL, and HSL in WAT and BAT.     

Effect of beta agonists on protein turnover in adipose tissue.

Chronic administration (21 days) of the beta agonist cimaterol to rats decreased epididymal fat by 27%, and inhibited in vitro rates of protein synthesis by 34% and net protein breakdown by 71% in adipose tissue. Likewise, incubation of rat adipose tissue with cimaterol and isoproterenol stimulated lipolysis, and inhibited protein synthesis and degradation. Thus, in addition to affecting muscle mass and lipid metabolism, beta agonists appear to slow rates of protein turnover in adipose tissue.     

Changes induced in adrenergic lipolysis by the administration of diethylstilboestrol, oestradiol and clomiphene

The authors studied changes in adrenergic lipolysis in the epididymal adipose tissue of rats to which diethylstilboestrol and oestradiol combined with the anti-oestrogen clomiphene were administered. The maximum lipid-mobilizing effect of isoprenaline was increased not only by subcutaneously administered diethylstilboestrol, but also by the highest dose of the antioestrogen clomiphene used (p.o., 200 micrograms.kg-1 b.w.). Under the given experimental conditions, with 4 1/2 h incubation of adipose tissue, clomiphene was also effective when added in vitro. Its own oestrogenic effect probably stimulated the lipid-mobilizing action of isoprenaline. On combining the administration of increasing doses of clomiphene (p.o., 1-5 days) with a constant dose of oestradiol (200 micrograms.kg-1, s.c. on the 8th day, i.e. 24 h before the actual experiment), changes in isoprenaline lipolysis depended on the dose of clomiphene. In low doses clomiphene inhibited the stimulating effect of subsequently administered oestradiol on isoprenaline-induced lipolysis, but in large doses (100 and 200 micrograms.kg-1 daily) it potentiated, together with oestradiol, the lipid-mobilizing effect of isoprenaline. The results show that the non-steroid oestrogen diethylstilboestrol and the antioestrogen clomiphene may be included among the hormones capable of altering the response of adipose tissue to sympathomimetics (isoprenaline). We attribute the fact that clomiphene acted either as an antagonist or as an agonist of oestradiol to its combined oestrogenic and anti-oestrogenic effects.     

Lipolysis in heart and adipose tissue: effects of inhibition of glycogenolysis and uncoupling of oxidative phosphorylation.

In the Langendorff heart, lipolysis is arrested when glycogenolysis is inhibited by the addition of 5-gluconolactone. Glucose partially overcomes the inhibition as well as uncoupling of oxidative phosphorylation by dinitrophenol. In isolated fat cells hormone-sensitive lipolysis is also inhibited by glycogenolysis inhibition and in these cells also, glucose addition overcomes the inhibition. In fat cells, uncoupling of oxidative phosphorylation does not stimulate lipolysis, probably because of the relatively low concentration of mitochondria in white adipose tissue. The data are interpreted that both in heart and adipose tissue cells, the removal of fatty acids produced by the endogenous lipase is the main stimulus for lipolysis. Attempts to generate in fat cells glycerol-3-phosphate by glycerogenesis from pyruvate or lactate led to the observation that not only these latter anions, but also propionate and acetate strongly stimulate lipolysis. It suggests that long-chain fatty acid removal from fat cells may be stimulated by anion exchange.     

Parathyroid hormone-induced lipolysis in human adipose tissue

Relative lipolytic activity of human parathyroid hormone-(1-34) (hPTH-(1-34], hPTH-(3-34), desamino-Ser1-hPTH-(1-34), and rat PTH-(1-34) was compared in human subcutaneous adipose tissues in vitro. Human PTH-(1-34), rat PTH-(1-34), and desamino-Ser1-hPTH-(1-34) stimulated in vitro lipolysis significantly above basal level at the concentration of 10(-6) M. Average increments of lipolytic rate were 2.39, 1.82, and 0.87 mumol/g per 2 hr, respectively, being significantly different among the three groups. On the other hand, hPTH-(3-34)-induced lipolytic rate was 0.83 +/- 0.18 mumol/g per 2 hr, not significantly different from the basal level (0.71 +/- 0.20 mumol/g per 2 hr). The effect of hPTH-(3-34) on glycerol release stimulated by hPTH-(1-34), isoproterenol, or forskolin was subsequently investigated. Human PTH-(3-34) produced a dose-dependent inhibition of hPTH-(1-34)-stimulated lipolysis. In contrast, isoproterenol- and forskolin-induced lipolytic rates were not influenced by hPTH-(3-34). The effect of propranolol on hPTH-(1-34)- or isoproterenol-induced lipolysis was also studied. Propranolol dose-dependently inhibited isoproterenol-induced lipolysis but had no effect on lipolysis stimulated by hPTH-(1-34). These results suggest that the amino acids at positions 1 (serine) and 2 (valine) of PTH are critical for the stimulation of lipolysis in human adipose tissue. Human PTH-(1-34) causes lipolysis after binding to receptors distinct from beta-adrenergic receptors of fat cells and possibly hPTH-(3-34) inhibits hPTH-(1-34)-stimulated lipolysis by competing at the level of PTH receptor.     

Apparent absence of alpha-2 adrenergic receptors from hamster brown adipocytes

The possible presence of α adrenergic control of lipolysis and cyclic AMP production in brown adipocytes of hamsters was studied in adipocytes isolated from interscapular, subscapular, cervical and axillary regions of normal male hamsters maintained at 25°C. Lipolysis activated by either 3-isobutyl-1-methyl xanthine or isoproterenol was unaffected by the presence of the α adrenergic selective agonists clonidine and methoxamine. Similarly, accumulation of cyclic AMP in response to β-receptor stimulation, alone or in combination with a methyl xanthine, was unaffected by clonidine or methoxamine. In contrast, both lipolysis and cyclic AMP accumulation in brown fat cells were effectively suppressed in the presence of nicotinic acid, prostaglandin E₁ or N⁶-phenylisopropyl adenosine. Accumulation of cyclic AMP in response to the mixed agonist norepinephrine was not influenced when cells were exposed to the alpha adrenergic blocking drugs yohimbine or tolazoline. These observations suggest that alpha-2 adrenergic receptors which are present on hamster white fat cells and control production of cyclic AMP and lipolysis are absent from hamster brown adipocytes. On the other hand, brown fat cells of this species appear to respond to a number of other inhibitory compounds in a manner not markedly different from that of white adipocytes.     

Growth and lipolysis of rat adipose tissue: effect of age, body weight, and food intake

The purpose of the present work was to study age- and weight-controlled rats to determine which is the primary factor in reducing the lipolytic response of free fat cells and which has the greater effect on the ratio of fat cells to nonfat cells in adipose tissue. The method for estimating fat cell and nonfat cell numbers is based on the analysis of adipose tissue and fat cell DNA and lipid. In adequately fed rats, epididymal adipocyte hyperplasia is complete between 9 and 14 wk of age. Chronic underfeeding delays, but does not eliminate, normal fat cell hyperplasia and is accompanied by a net loss in the nonfat cell population. During 9-14 wk of age, rat epididymal adipose tissue enlarges mainly through adipocyte hypertrophy. Total fat cells from the epididymal adipose tissue of control rats represent only 20-23% of the total cell population. Chronic underfeeding increases the percentage of fat cells in the fat pad from 23 to 28%. Noradrenaline-stimulated lipolysis is proportional to fat cell numbers but is inhibited when fat cell lipid increases to over 80% of fat pad wet weight. Rat age is apparently not primarily responsible for the decreased noradrenaline-stimulated lipolysis in fat cells of 350-g rats in vitro.